Alexander M. Nauth

A Highly Active System for the Metal-Free Aerobic Photocyanation of Tertiary Amines with Visible Light: Application to the Synthesis of Tetraponerines and Crispine A.

A highly efficient metal-free catalytic system for the aerobic photocyanation of tertiary amines with visible light is reported. The use of air as terminal oxidant offers an improved safety profile compared with pure oxygen, the used compact fluorescent lamp (CFL) light sources are highly economical, and no halogenated solvents are required. This system not only proves to be effective for a wide variety of trialkylamines, pharmaceuticals, and alkaloids but remarkably also allows the lowest catalyst loading (0.00001 mol% or 0.1 ppm) ever reported for an organic dye. Bruylants reactions and C-alkylation/decyanations were performed on the obtained α-aminonitriles to demonstrate the postfunctionalization of complex molecules. The catalytic system is furthermore applied in the short and effective syntheses of the alkaloids (±)-crispine A and the tetraponerines T7 and T8.

Transition-Metal-Free Decarboxylative Photoredox Coupling of Carboxylic Acids and Alcohols with Aromatic Nitriles

A transition-metal-free protocol for the redox-neutral light-induced decarboxylative coupling of carboxylic acids with (hetero)aromatic nitriles at ambient temperature is presented. A broad scope of acids and nitriles is accepted, and alcohols can be coupled in a similar fashion through their oxalate half esters. Various inexpensive sources of UV light and even sunlight can be used to achieve this C-C bond formation proceeding through a free radical mechanism.

An efficient and practical synthesis of [2-11C]indole via superfast nucleophilic [11C]cyanation and RANEY® Nickel catalyzed reductive cyclization

A rapid method for the synthesis of carbon-11 radiolabeled indole was developed using a sub-nanomolar quantity of no-carrier-added [(11)C]cyanide as radio-precursor. Based upon a reported synthesis of 2-(2-nitrophenyl)acetonitrile (), a highly reactive substrate 2-nitrobenzyl bromide () was evaluated for nucleophilic [(11)C]cyanation. Additionally, related reaction conditions were explored with the goal of obtaining of highly reactive 2-(2-nitrophenyl)-[1-(11)C]acetonitrile () while inhibiting its rapid conversion to 2,3-bis(2-nitrophenyl)-[1-(11)C]propanenitrile (). Next, a RANEY® Nickel catalyzed reductive cyclization method was utilized for synthesizing the desired [2-(11)C]indole with hydrazinium monoformate as the active reducing agent. Extensive and iterative screening of basicity, temperature and stoichiometry was required to overcome the large stoichiometry bias that favored 2-nitrobenzylbromide () over [(11)C]cyanide, which both caused further alkylation of the desired nitrile and poisoned the RANEY® Nickel catalyst. The result is an efficient two-step, streamlined method to reliably synthesize [2-(11)C]indole with an entire radiochemical yield of 21 ± 2.2% (n = 5, ranging from 18-24%). The radiochemical purity of the final product was >98% and specific activity was 176 ± 24.8 GBq μmol(-1) (n = 5, ranging from 141-204 GBq μmol(-1)). The total radiosynthesis time including product purification by semi-preparative HPLC was 50-55 min from end of cyclotron bombardment.

Synthesis of α-aminonitriles using aliphatic nitriles, α-amino acids, and hexacyanoferrate as universally applicable non-toxic cyanide sources

In cyanation reactions, the cyanide source is often directly added to the reaction mixture, which restricts the choice of conditions. The spatial separation of cyanide release and consumption offers higher flexibility instead. Such a setting was used for the cyanation of iminium ions with a variety of different easy-to-handle HCN sources such as hexacyanoferrate, acetonitrile or α-amino acids. The latter substrates were first converted to their corresponding nitriles through oxidative decarboxylation. While glycine directly furnishes HCN in the oxidation step, the aliphatic nitriles derived from α-substituted amino acids can be further converted into the corresponding cyanohydrins in an oxidative C–H functionalization. Mn(OAc)2 was found to catalyze the efficient release of HCN from these cyanohydrins or from acetone cyanohydrin under acidic conditions and, in combination with the two previous transformations, permits the use of protein biomass as a non-toxic source of HCN.

TiO2 Nanoparticles Functionalized with Non-innocent Ligands Allow Oxidative Photocyanation of Amines with Visible/Near-Infrared Photons

Photosynthesis is an efficient mechanism for converting solar light energy into chemical energy. We report on a strategy for the aerobic photocyanation of tertiary amines with visible and near-infrared (NIR) light. Panchromatic sensitization was achieved by functionalizing TiO2 with a 2-methylisoquinolinium chromophore, which captures essential features of the extended π-system of 2,7-diazapyrenium (DAP2+) dications or graphitic carbon nitride. Two phenolic hydroxy groups make this ligand highly redox-active and allow for efficient surface binding and enhanced electron transfer to the TiO2 surface. Non-innocent ligands have energetically accessible levels that allow redox reactions to change their charge state. Thus, the conduction band is sufficiently high to allow photochemical reduction of molecular oxygen, even with NIR light. The catalytic performance (up to 90% chemical yield for NIR excitation) of this panchromatic photocatalyst is superior to that of all photocatalysts known thus far, enabling oxidative cyanation reactions to the corresponding α-cyanated amines to proceed with high efficiency. The discovery that the surface-binding of redox-active ligands exhibits enhanced light-harvesting in the red and NIR region opens up the way to improve the overall yields in heterogeneous photocatalytic reactions. Thus, this class of functionalized semiconductors provides the basis for the design of new photocatalysts containing non-innocent donor ligands. This should increase the molar extinction coefficient, permitting a reduction of nanoparticle catalyst concentration and an increase of the chemical yields in photocatalytic reactions.